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Mechanisms of survival of protozoan parasites in mononuclear phagocytes

Published online by Cambridge University Press:  23 August 2011

J. Mauel
J. Mauel
Affiliation:
WHO Laboratories, Institute of Biochemistry, Ch. des Boveresses, CH-1066 Epalinges, Switzerland
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Summary

The understanding of the mechanisms whereby intracellular parasites counteract the microbicidal processes of macrophages has progressed considerably in recent years. Various factors contribute to intracellular parasite destruction; from a biochemical standpoint, particularly important is the oxidative burst triggered by phagocytosis and by macrophage ‘activation’, that leads to the generation of toxic metabolites of oxygen. At the ultrastructural level, fusion of the parasitophorous vacuole with surrounding lysosomes appears to be a pre-requisite for the final digestion and elimination of the infecting microorganisms. The counter-measures evolved by microorganisms to escape intracellular destruction are best illustrated by studies in vitro on the interaction of parasites of the Leishmania, Toxoplasma and Trypanosoma spp. with mononuclear phagocytes. Some microbes are able to inhibit the fusion of phagosomes with lysosomes, thus avoiding the potentially harmful action of lysosomal hydrolases. Other microorganisms are able to resist the effects of such enzymes, perhaps by secreting inhibitory substances. Others still avoid lysosomes by leaving the phagocytic vacuole, to reach the cytoplasmic matrix where their development is unhindered. Particularly critical is the capacity of certain parasites to subvert the lethal effects of the oxidative burst. This can be achieved either by failing to evoke this metabolic response, or by producing scavengers that can detoxify harmful oxygen metabolites. Intracellular death or survival will thus depend on a delicate balance between the potency of macrophage cidal mechanisms, and the efficacy of the protective measures evolved by the infecting agents.

Type
Research Article
Information
Parasitology , Volume 88 , Issue 4: Symposia of the British Society for Parasitology Volume 21: Parasite evasion of the immune response , August 1984 , pp. 579 - 592
Copyright
Copyright © Cambridge University Press 1984

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References

REFERENCES

Alexander, J. (1975). Effect of the antiphagocytic agent Cytochalasin B on macrophage invasion by Leishmania mexicana promastigotes and Trypanosoma cruzi epimastigotes. Journal of Protozoology 22, 237–40.CrossRefGoogle ScholarPubMed
Alexander, J. (1981). L. mexicana: Inhibition and stimulation of phagosome-lysosome fusion in infected macrophages. Experimental Parasitology 52, 261–70.CrossRefGoogle Scholar
Alexander, J. & Vickerman, K. (1975). Fusion of host cell secondary lysosomes with the parasitophorous vacuole of L. mexicano-infected macrophages. Journal of Protozoology 22, 502–8.CrossRefGoogle Scholar
Ardehali, S. M., Khoubyar, K. & Rezai, H. R. (1979). Studies on the effect of the antiphagocytic agent Cytochalasin B on Leishmania-macrophage interaction. Acta Tropica 36, 15–19.Google ScholarPubMed
Armstrong, J. A. & D'arcy Hart, P. (1971). Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of phagosomes with lysosomes. Journal of Experimental Medicine 134, 134–713.CrossRefGoogle ScholarPubMed
Armstrong, J. A. & D'arcy, Hart P. (1975). Phagosome-lysosome interactions in cultured macrophages infected with virulent tubercle bacilli. Reversal of the usual non-fusion pattern and observations on bacterial survival. Journal of Experimental Medicine 142, 142–1.CrossRefGoogle Scholar
Avila, J. L. & Convit, J. (1976). Physicochemical characteristics of the glycosamino-glycanlysosomal enzyme interaction in vitro. The Biochemical Journal 160, 129–36.CrossRefGoogle ScholarPubMed
Babior, B. M. (1978). Oxygen-dependent microbial killing by phagocytes. New England Journal of Medicine 298, 659–68, 721–5.CrossRefGoogle ScholarPubMed
Badwey, J. A. & Karnovsky, M. L. (1980). Active oxygen species and the function of phagocytic leukocytes. Annual Review of Biochemistry 49, 695–726.CrossRefGoogle ScholarPubMed
Behin, R., Mauel, J., Biroum-Noerjasin, & Rowe, D. S. (1975). Mechanisms of protective immunity in experimental cutaneous leishmaniasis of the guinea-pig II. Selective destruction of different Leishmania species in activated guinea-pig and mouse macrophages. Clinical and Experimental Immunology 20, 351–60.Google ScholarPubMed
Behin, R., Mauel, J. & Sordat, B. (1979). Leishmania tropica: pathogenicity and in vitro macrophage function in strains of inbred mice. Experimental Parasitology 48, 81–91.CrossRefGoogle ScholarPubMed
Bellavite, P., Breton, G., Dri, P. & Soranzo, R. (1981). Enzymatic basis of the respiratory burst of guinea-pig resident peritoneal macrophages. Journal of the Reticuloendothelial Society 29, 47–60.Google ScholarPubMed
Benchimol, M. & De SOUZA, W. (1981). Leishmania mexicana amazonensis: attachment to the membrane of the phagocytic vacuole of macrophages in vitro. Zeitschrift für Parasitenkunde 66, 25–9.CrossRefGoogle Scholar
Bebman, J. D., Dwyer, D. M. & Wyler, D. J. (1979). Multiplication of Leishmania in human macrophages in vitro. Infection and Immunity 26, 375–9.Google Scholar
Buchmüller, Y. & Mauel, J. (1981). Studies on the mechanisms of macrophage activation: possible involvement of oxygen metabolites in killing of Leishmania enriettii by activated mouse macrophages. Journal of the Reticulo-endothelial Society 29, 181–92.Google Scholar
Chang, K. P. (1978). Leishmania infection of human skin fibroblasts in vitro: absence of phagolysosomal fusion after induced phagocytosis of promastigotes, and their intracellular transformation. American Journal of Tropical Medicine and Hygiene 27, 1084–96.CrossRefGoogle ScholarPubMed
Chang, K. P. (1979). Leishmania donovani: promastigote—macrophage surface interactions in vitro. Experimental Parasitology 48, 175–89.CrossRefGoogle ScholarPubMed
Chang, K. P. (1980). Endocytosis of Leishmania-infected macrophages. Fluorometry of pinocytic rate, lysosome—phagosome fusion and intralysosomal pH. In The Host—Invader Interplay (ed. Bossche, H. Van den), pp. 231–4. Amsterdam: Elsevier-North Holland.Google Scholar
Chang, K. P. & Dwyer, D. M. (1976). Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science 193, 678–80.CrossRefGoogle ScholarPubMed
Chang, K. P. & Dwyer, D. M. (1978). Leishmania donovani-hamster macrophage interactions in vitro: cell entry, intracellular survival and multiplication of amastigotes. Journal of Experimental Medicine 147, 515–30.CrossRefGoogle ScholarPubMed
Coombs, G. H. (1982). Proteinases of Leishmania mexicana and other flagellate protozoa. Parasitology 84, 149–55.CrossRefGoogle ScholarPubMed
D'abcy Hart, P. & Young, M. R. (1978). Manipulation of the phagosome—lysosome fusion response in cultured macrophages. Enhancement of fusion by chloroquine and other amines. Experimental Cell Research 114, 486–90.CrossRefGoogle ScholarPubMed
Davis-Scibienski, C. & Beaman, B. L. (1980). Interaction of Nocardia asteroides with rabbit alveolar macrophages: association of virulence, viability, ultrastructural damage, and phagosome—lysosome fusion. Infection and Immunity 28, 610–19.CrossRefGoogle ScholarPubMed
Draper, P. & Rees, R. J. W. (1970). Electron-transparent zone of mycobacteria may be a defence mechanism. Nature, London 228, 860–1.CrossRefGoogle ScholarPubMed
Ebert, F., Enriquez, G. L. & Mühlpfordt, H. (1976). Electron microscopic studies of the phagocytosis of Leishmania donovani by hamster peritoneal macrophages and its lysosomal activity in vivo. Behring Institut Mitteilungen 60, 65–74.Google Scholar
Elon, J., Bradley, D. J. & Freeman, J. C. (1980). Leishmania donovani: action of excreted factor on hydrolytic enzyme activity of macrophages from mice with genetically different resistance to infection. Experimental Parasitology 49, 167–74.CrossRefGoogle ScholarPubMed
Forman, H. J., Nelson, J. & Fischer, A. B. (1980). Rat alveolar macrophages require NADPH for superoxide production in the respiratory burst. Journal of Biological Chemistry 255, 9879–83.CrossRefGoogle ScholarPubMed
Glauert, A. M., Fell, H. B. & Dingle, J. T. (1969). Endocytosis of sugars in embryonic skeletal tissues in organ culture. II. Effect of sucrose on cellular fine structure. Journal of Cell Science 4, 105–31.CrossRefGoogle ScholarPubMed
Gordon, A. H., D'arcy Hart, P. & Young, M. R. (1980). Ammonia inhibits phagosome-lyso-some fusion in macrophages. Nature London 286, 79–80.CrossRefGoogle ScholarPubMed
Goren, M. B., D'arcy Hart, P., Young, M. R. & Armstrong, J. A. (1976). Prevention of phagosome—lysosome fusion in cultured macrophages by sulfatides of Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences, USA 73, 2510–14.CrossRefGoogle ScholarPubMed
Griffin, F. M., Griffin, J. A., Leider, J. E. & Silverstein, S. C. (1975). Studies on the mechanisms of phagocytosis. Journal of Experimental Medicine 142, 1263–82.CrossRefGoogle ScholarPubMed
Hafizi, A. & Moddaber, F. Z. (1978). Effect of cyclophosphamide on Toxoplasma gondii infection: reversal of the eifect by passive immunization. Clinical and Experimental Immunology 23, 389–94.Google Scholar
Haidaris, C. G. & Bonventre, P. F. (1982). A role for oxygen-dependent mechanisms in killing of Leishmania donovani tissue forms by activated macrophages. Journal of Immunology 129, 850–5.CrossRefGoogle ScholarPubMed
Handman, E. & Greenblatt, C. L. (1977). Promotion of leishmanial infection in non-permissive host-macrophages by conditioned medium. Zeitschrift für Parasitenkunde 53, 143–7.CrossRefGoogle ScholarPubMed
Handman, E., Ceredig, R. & Mitchell, G. F. (1979). Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages. Australian Journal of Experimental Biology and Medical Sciences 57, 9–30.CrossRefGoogle ScholarPubMed
Johnston, R. B. (1978). Oxygen metabolism and the microbicidal activity of macrophages. Federation Proceedings 37, 2759–64.Google ScholarPubMed
Kress, Y., Bloom, B. R., Wittner, M., Rowen, A. & Tanowitz, H. (1975). Resistance of Trypanosoma cruzi to killing by macrophages. Nature, London 257, 394–6.CrossRefGoogle ScholarPubMed
Kutish, G. F. & Janovy, J. (1981) Inhibition of in vitro macrophage digestion capacity by infection with Leishmania donovani. Journal of Parasitology 67, 457–62.CrossRefGoogle ScholarPubMed
Lewis, D. H. & Peters, W. (1977). The resistance of intracellular Leishmania parasites to digestion by lysosomal enzymes. Annals of Tropical Medicine and Parasitology 71, 295–312.CrossRefGoogle ScholarPubMed
Mauel, J. (1982). Effector and escape mechanisms in host—parasite relationships. In Progress in Allergy, vol. 31 (ed. Kallos, P.), pp. 1–75. Basel: Karger.Google Scholar
Mauel, J., Buchmüller, Y. & Behin, R. (1978). Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes. Journal of Experimental Medicine 148, 393–407.CrossRefGoogle ScholarPubMed
Murray, H. W. (1981a). Susceptibility of Leishmania to oxygen intermediates and killing by normal macrophages. Journal of Experimental Medicine 153, 1302–15.CrossRefGoogle ScholarPubMed
Murray, H. W. (1981b). Interaction of Leishmania with a macrophage cell line. Journal of Experimental Medicine 153, 1690–5.CrossRefGoogle ScholarPubMed
Murray, H. W. & Cohn, Z. A. (1979). Macrophage oxygen-dependent antimicrobial activity. I. Susceptibility of Toxoplasma gondii to oxygen intermediates. Journal of Experimental Medicine 150, 938–49.CrossRefGoogle ScholarPubMed
Murray, H. W. & Cohn, Z. A. (1980). Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation. Journal of Experimental Medicine 152, 1596–609.CrossRefGoogle ScholarPubMed
Murray, H. W., Juangbhanich, C. W., Nathan, C. F. & Cohn, Z. A. (1979). Macrophage oxygen-dependent antimicrobial activity. II. The role of oxygen intermediates. Journal of Experimental Medicine 150, 950–64.CrossRefGoogle ScholarPubMed
Nathan, C. F., Nogueira, N., Juangbhanich, C. W., Ellis, J. & Cohn, Z. A. (1979). Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi. Journal of Experimental Medicine 149, 1056–68.CrossRefGoogle ScholarPubMed
Nogueira, N. & Cohn, Z. A. (1976). Trypanosoma cruzi: mechanism of entry and intracellular fate in mammalian cells. Journal of Experimental Medicine 143, 1402–20.CrossRefGoogle ScholarPubMed
Ohkuma, S. & Poole, B. (1978). Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proceedings of the National Academy of Sciences, USA 75, 3327–31.CrossRefGoogle ScholarPubMed
Pearson, R. L., Harcus, J. L., Symes, P. H., Romito, R. & Donowitz, G. R. (1982). Failure of the phagocytic oxidative response to protect human monocyte-derived macrophages from infection by Leishmania donovani. Journal of Immunology 129, 1282–6.CrossRefGoogle ScholarPubMed
Preston, P. M. & Dumonde, D. C. (1976). Immunology of clinical and experimental Leish-maniasis. In Immunology of Parasitic Infections (ed. Cohen, S. and Sadun, E. H.), pp. 167–202. Oxford: Blackwell Scientific Publications.Google Scholar
Schnur, L. F., Zuckerman, A. & Greenblatt, C. L. (1972). Leishmanial serotypes as distinguished by gel diffusion of factors excreted in vitro and in vivo. Israel Journal of Medical Sciences 8, 932–42.Google ScholarPubMed
Seglen, P. O., Grinde, B. & Solheim, A. E. (1979). Inhibition of the lysosomal pathway of protein degradation in isolated rat hepatocytes by ammonia, methylamine, chloroquine and leupeptin. European Journal of Biochemistry 95, 215–25.CrossRefGoogle ScholarPubMed
Sethi, K. K., Eudo, T. & Brandis, H. (1981). Toxoplasma gondii trophozoites precoated with specific monoclonal antibodies cannot survive within normal murine macrophages. Immunology Letters 2, 343–6.CrossRefGoogle Scholar
Shepherd, V. L., Stahl, P. D., Bernd, P. & Rabinovitch, M. (1983). Receptor-mediated entry of β-glucuronidase into the parasitophorous vacuoles of macrophages infected with Leishmania mexicana amazonensis. Journal of Experimental Medicine 157, 1471–82.CrossRefGoogle ScholarPubMed
Slutzky, G. M. & Greenblatt, C. L. (1979). Analysis by SDS-polyacrylamidegel electrophoresis of an immunologically active factor of Leishmania tropica from growth media, promastigotes and infected macrophages. Biochemical Medicine 21, 70–7.CrossRefGoogle Scholar
Sordat, B. & Behin, R. (1977). Cutaneous leishmaniasis of the guinea pig: a sequential study by light and electron microscopy. In Ecologie des Leishmanioses, pp. 87–93. Paris: INSERM.Google Scholar
Tanowitz, H., Wittner, M., Kress, Y. & Bloom, B. R. (1975). Studies of in vitro infection by T. cruzi. I. Ultrastructural studies on the invasion of macrophages and L cells. American Journal of Tropical Medicine and Hygiene 24, 25–33.CrossRefGoogle Scholar
Weidemann, M. J., Smith, R., Haeney, T. & Alaudeen, S. (1980). On the mechanism of the generation of chemiluminescence by macrophages. Behring Institut Mitteilungen 65, 42–54.Google Scholar
Wilson, C. B., Tsai, V. & Remington, J. S. (1980). Failure to trigger the oxidative metabolic burst by normal macrophages. Possible mechanism for survival of intracellular pathogens. Journal of Experimental Medicine 151, 328–46.CrossRefGoogle ScholarPubMed